Closing the knowledge gap on the composition of the asbestos bodies.

Asbestos bodies (AB) form in the lungs as a result of a biomineralization process initiated by the alveolar macrophages in the attempt to remove asbestos. During this process, organic and inorganic material deposit on the foreign fibers forming a Fe-rich coating. The AB start to form in months, thus quickly becoming the actual interface between asbestos and the lung tissue. Therefore, revealing their composition, and, in particular, the chemical form of Fe, which is the major component of the AB, is essential to assess their possible role in the pathogenesis of asbestos-related diseases. In this work we report the result of the first x-ray diffraction measurements performed on single AB embedded in the lung tissue samples of former asbestos plant workers. The combination with x-ray absorption spectroscopy data allowed to unambiguously reveal that Fe is present in the AB in the form of two Fe-oxy(hydroxides): ferrihydrite and goethite. The presence of goethite, which can be explained in terms of the transformation of ferrihydrite (a metastable phase) due to the acidic conditions induced by the alveolar macrophages in their attempt to phagocytose the fibers, has toxicological implications that are discussed in the paper.

Genetic diversity and population structure of a rare flowering tree endemic to Appalachia, Stewartia ovata.

Stewartia ovata (cav.) Weatherby, commonly known as mountain stewartia, is an understory tree native to the southeastern United States (U.S.). This relatively rare species occurs in isolated populations in Virginia, Kentucky, Tennessee, North Carolina, South Carolina, Georgia, Alabama, and Mississippi. As a species, S. ovata has largely been overlooked, and limited information is available regarding its ecology, which presents obstacles to conservation efforts. Stewartia ovata has vibrant, large white flowers that bloom in summer with a variety of filament colors, suggesting potential horticultural traits prized by ornamental industry. However, S. ovata is relatively slow growing and, due to long seed dormancy, propagation is challenging with limited success rates. This has created a need to assess the present genetic diversity in S. ovata populations to inform potential conservation and restoration of the species. Here, we employ a genotyping-by-sequencing (GBS) approach to characterize the spatial distribution and genetic diversity of S. ovata in the southern Appalachia region of the eastern United States. A total of 4475 single nucleotide polymorphisms (SNPs) were identified across 147 individuals from 11 collection sites. Our results indicate low genetic diversity (He = 0.216), the presence of population structure (K = 2), limited differentiation (F ST = 0.039), and high gene flow (Nm = 6.16) between our subpopulations. Principal component analysis corroborated the findings of STRUCTURE, confirming the presence of two distinct S. ovata subpopulations. One subpopulation mainly contains genotypes from the Cumberland Plateau, Tennessee, while the other consists of genotypes present in the Great Smoky Mountain ranges in Tennessee, North Carolina, and portions of Nantahala, Chattahoochee-Oconee national forests in Georgia, highlighting that elevation likely plays a major role in its distribution. Our results further suggested low inbreeding coefficient (F IS = 0.070), which is expected with an outcrossing tree species. This research further provides necessary insight into extant subpopulations and has generated valuable resources needed for conservation efforts of S. ovata.

In vitro studies of histone glycation.

Reductive amination of histone H1 by [U-14C]glucose was performed in the presence of sodium cyanoborohydride and was approximately proportional to the glucose concentration. Lysine was the principal amino acid substituted. Glycation also occurred in the absence of cyanoborohydride. Browning reactions of histones were monitored by delta A 325 whereby it was shown that glucose 6-phosphate was more reactive than glucose and that each of the histone fractions reacted with glucose 6-phosphate giving the browning reaction.

Isotopic analysis of uranium in tree bark by ICP mass spectrometry: a strategy for assessment of airborne contamination

Isotopic analysis of uranium in tree bark by ICP mass spectrometry is proposed as a new measurement strategy for monitoring airborne contamination and for discrimination of nuclear and nonnuclear emission sources. A quadrupole-based ICP mass spectrometer equipped with a microconcentric nebulizer and membrane desolvator was used to provide high-sensitivity measurement. The limit of detection for uranium (238U) was 0.004 ng L(-1). Measurement precision (235U/238U) was between 0.2 and 0.5% RSD for isotopic SRMs (U005 and U015; concentration, 1 microg L(-1)) and ranged from 0.4 to 3.1% RSD for tree bark extracts (U concentration, 0.03-0.08 microg L(-1)). Bark samples collected from the Peak District National Park in Derbyshire (U.K.) exhibited a natural 235U/238U isotope ratio value (0.0072) whereas samples from Sellafield, West Cumbria (U.K.) showed depletion in 235U (235U/238U = 0.0053-0.0064).

Minimal pathologic changes of the lung and asbestos exposure.

A group of 199 autopsy subjects was investigated for minimal pathologic pulmonary changes possibly resulting from asbestos exposure. According to the standards proposed by the Pneumoconiosis Committee of the College of American Pathologists, features consistent with asbestosis grade 1 (AG1) include findings of bilateral pleural plaques, high concentrations of asbestos bodies (ABs) in digested lung tissue, and a history of occupational risk. Similar changes without evidence of ABs on histologic section and referred to as small airway lesions (SALs) present a less well-correlated association. In this study, SALs showed significant differences when compared with the features observed in subjects without possible asbestos-related pulmonary fibrotic changes. Minimal bronchioloalveolar fibrotic changes with concomitant presence of ABs can be considered a mild pneumoconiotic lesion (AG1), and SALs may be regarded as an additional indicator of asbestos exposure.

Malignant peritoneal mesothelioma in a 17-year-old boy with evidence of previous exposure to chrysotile and tremolite asbestos.

We describe a case of malignant peritoneal mesothelioma arising in a 17-year-old boy. The diagnosis was based on a comprehensive study including light microscopy, histochemistry, immunohistochemistry, evaluation of the clinical course, and autopsy examination. Analytical transmission electron microscopy showed a concentration of 510,000 asbestos fibers/g dry lung tissue. The fibers were represented by chrysotile (62%) and tremolite (38%) asbestos. About 40% of the total fibers were longer than 5 microns. The presence of tremolite fibers was probably due to environmental exposure to contaminated cosmetic talc. This is the first reported case of pathologically proven exposure to asbestos dust in malignant mesothelioma of childhood and adolescence.

Ostial stenosis of the left main coronary artery in a young woman 10 years after radiation therapy.

A 26-year-old woman developed critical stenosis of the left main coronary artery 10 years after radiation treatment for Hodgkins disease. She was operated on but died in the immediate postoperative period. At autopsy the pathological findings were indistinguishable from those described in "typical" atherosclerotic plaques.

Quantitative assessment of histological changes in chronic gastritis after eradication of Helicobacter pylori.

AIMS: To evaluate the effect of 10 day triple treatment on H pylori eradication and associated gastritis. METHODS: Fifty patients with H pylori positive non-ulcer dyspepsia were treated for 10 days with amoxicillin, tinidazole, and bismuth salts. Histological examination of the antral mucosa was performed before (T0), six weeks (T1), and six months (T2) after treatment. The new Sydney classification of gastritis was used, using a score from 0 to 3 to grade degree of inflammation, atrophy, activity (intraepithelial or lamina propria damage) and H pylori. RESULTS: At T0 all patients had chronic active gastritis. Lymphoid follicules were present in 12 cases. At T1 33 patients were H pylori negative: the score showed a decrease of activity (from 2.5 to 0.54). The result was confirmed at T2 (mean score 0.22). Inflammation decreased from 1.8 to 1.4 at T2. Only one case of follicular gastritis was observed. In H pylori positive patients the scores did not show significant modifications. CONCLUSIONS: Ten day triple treatment is effective in eradicating H pylori in 69% of cases, causing a decrease of the total score for gastritis. Activity, defined by polymorph infiltration, was promptly reduced when H pylori was eradicated. There was a trend to a reduction in inflammation, but atrophy was irreversible.

Light microscopic and immunohistochemical evaluation of vascular and neural invasion in colorectal cancer.

One hundred and sixty consecutive surgically removed colorectal carcinomas were investigated on histological sections stained with Hematoxylin and Eosin (H & E). Vascular and neural neoplastic invasion was found in 49 (30.6%) and 50 (31.3%) patients. In addition, immunohistochemical investigation was performed on step sections to those stained with H & E in the first 50 patients, using anti-human Factor VIII related antigen, anti-actin and anti-protein S 100 antisera. The percentages of positive cases for vascular invasion in this group of 50 patients were 20% on H & E sections and 62% on those stained with anti-Factor VIII and anti-actin antisera. Neural infiltration was identified in 14% of cases on H & E sections and in 70% of cases on anti-protein S 100 treated sections. Since vascular and neural infiltration are known to be ominous prognostic factors, their identification has great clinical relevance. The use of these simple immunohistochemical stains, using readily available antisera on formalin-fixed material, is recommended as routine procedure in surgical pathology laboratories.

Atypical changes of respiratory epithelium after heart-lung transplantation. A case report.

Atypical changes of bronchial respiratory epithelium in a combined heart-lung transplantation recipient are reported. The occurrence of diffuse hyperplasia, squamous metaplasia and dysplasia with foci of disorganized structure of the respiratory epithelium is described. These epithelial changes in the bronchial tree were considered to have arisen after transplantation; their origin, significance and possible evolution are discussed.

Coated and uncoated lung mineral fibres in subjects with and without pleural plaques at autopsy.

The lung concentration of coated and uncoated mineral fibres of more than 10 micron in length was determined by light microscopy in 57 autopsied subjects (23 out of which professionally exposed to asbestos) with pleural plaques but no other asbestos-related diseases. Comparisons were made with 57 controls matched for sex, age and smoking habits, who did not show any asbestos-associated diseases or history of previous occupational exposure. Subjects with pleural plaques had a median concentration of coated fibres consistently greater than that observed in those without. However, no substantial differences were found between the two studied groups when uncoated and total fibres were considered. The present study suggests that the factors related to the fibre coating and to the pleural plaque formation may be indirectly connected, but not necessarily restricted to the number and nature of the fibres, or to the professional or environmental conditions of exposure.

Role of iron in asbestos-body-induced oxidant radical generation.

Asbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TBA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thiourea (DMTU) and mannitol (MN) also effectively blocked TBA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TBA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. In the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.

Hyaline splenic and hepatic plaques. Correlation with cirrhosis, pulmonary tuberculosis, and asbestos exposure.

Nine hundred twenty-five unselected autopsies were investigated for the presence or absence of hyaline peritoneal (splenic or hepatic) plaques, hyaline pleural plaques, asbestos, liver cirrhosis, heart failure, previous peritoneal dialysis or abdominal surgery, chronic peritonitis, splenomegaly, splenic infarcts, and pulmonary or abdominal tuberculosis. Lung asbestos body concentrations were calculated in 570 subjects. Peritoneal plaques were recorded in 163 cases. In both univariate and multivariate analyses, they were associated with cirrhosis, pulmonary nonactive tuberculosis, pleural plaques, and asbestosis. Association with asbestos body counts was also found, with a significant trend. Peritoneal plaques were described long ago in different pathologic conditions, for some of which (cirrhosis and nonactive pulmonary tuberculosis) the association is confirmed by the present analysis. It is suggested that they are significantly associated, moreover, with indicators of asbestos exposure.

Airborne emission of enriched uranium at Tokai-mura, Japan.

A new strategy for characterisation of airborne uranium contamination based on elemental/isotopic analysis of tree bark is described. Bark samples collected at Tokai-mura (Japan) were subjected to high sensitivity ICP mass spectrometric analysis; for control purposes, samples from the remote Yakushima island (Southern Japan) and central Tokyo were also analysed. The uranium contents of tree bark for Tokyo and Yakushima were of similar magnitude to that at Tokai-mura (U, 0.01-1.0 microg/g - all samples), however, there were marked differences in isotope ratio values between the sites. Whereas natural uranium isotope ratio values (235U/238U, 0.0072) were observed for Yakushima and Tokyo, non-natural and natural signatures (235U/238U, 0.00697-0.01448) were realised at Tokai-mura. These findings are consistent with the release of enriched uranium at Tokai-mura.

Airborne uranium contamination--as revealed through elemental and isotopic analysis of tree bark.

A new strategy for characterisation of airborne uranium contamination based on ICP mass spectrometric analysis of tree bark is described. The uranium content of tree barks (50 samples) obtained from diverse locations (remote, rural, industrial) varied over almost four orders of magnitude (0.001-8.3 micrograms/g U) with maximum concentrations recorded in the vicinity of a nuclear fuel fabrication plant (0.70-8.3 micrograms/g U). Elevated concentrations were also observed near a coal-fired power station (0.25-0.38 microgram/g U). Isotopic analysis revealed significant deviation from the natural uranium isotope ratio (235U/238U, 0.00725) at four nuclear installations (235U/238U, 0.0055-0.0097). These findings indicate that tree bark serves as an effective biomonitor for uranium and, with isotopic analysis, discrimination between nuclear and non-nuclear emissions is realised.

Reduction of AIDS risk among 41 heroin addicted female street prostitutes: effects of free methadone maintenance.

Interviews were previously conducted with 72 heroin-addicted female street prostitutes who spread HIV by sharing injection paraphernalia and engaging in unprotected sex with multiple male customers. Most were willing to enroll in free methadone maintenance if made available. Forty-one female addict-prostitutes subsequently entered free methadone maintenance. Twenty-five remained in treatment after one year. Their personal income from prostitution and other crime was reduced 58%; income from legal sources increased 86%. Total urinalyses positive for non-prescribed drugs decreased from 80% on admission to 51%. This pilot study validates the attraction of free methadone maintenance and concomitant reduction of illegal drug use and prostitution, two predictors of HIV infection. However, close supervision and effective counseling and rehabilitative services provided by better trained staff are required for successful outcomes among addict-prostitutes in methadone maintenance.

Screening of autopsy populations for previous occupational exposure to asbestos.

A screening procedure to select, in autopsy populations, subjects having a major likelihood of previous occupational exposure to asbestos is described. To test our necropsy population we searched for pleural plaques (PPs); the optical count of both lung asbestos bodies (ABs) and uncoated mineral fibers (UMFs) at least 10 microns in length was recorded. In the adult autopsy population studied in the Turin area, the predictive value given by a positive test for large-size PPs (mostly bilateral) was about 55%. This level of probability did not rise in relation to the AB counts, whereas an increase to over 75% was observed if more than 10,000 UMFs/g dry lung were present. In subjects without PPs or with small-size plaque lesions (mostly unilateral), predictive values of positive tests were 20 to 30% when ABs and UMFs were found to be below 100 and 10,000/g, respectively, and increased to approximately 40% if the AB count exceeded 500/g and to almost 70% for an UMF count above 100,000/g. In subjects without PPs or with small-size plaque lesions, the probability of being nonexposed was greater than 90% if neither ABs nor UMFs were found. This autopsy screening may be a reliable tool in selecting cases most probably related to occupational exposure.

[Lung cancers attributable to asbestos on a pathological basis]. / Carcinomi polmonari attribuibili ad asbesto su base patologica.

More than 1,000 asbestos bodies/gram dry weight (AB/gdw) were found by light microscopy in lung tissues, out of 429 non selected cases of pulmonary carcinoma (264 from surgery and 165 from autopsy). Asbestosis was detected by histology in 28% of the cases with AB > 1,000/gdw (in 19% of the surgical cases, and in 38% of the autopsy cases). A proportion of 4% of the total cases may be related to asbestos exposure.

[An etiological definition of a case of mixed pneumoconiosis due to silicates and coal in the absence of anamnestic data]. / Definizione etiologica di un caso di pneumoconiosi mista da silicati e carbone in assenza del dato anamnestico.

A case of pneumoconiosis with unknown occupational history was examined both pathologically and mineralogically by means of a variety of techniques, including analytical scanning and transmission electron microscopy with electron diffraction and energy dispersive x-ray analysis, and electron resonance spectroscopy. The pathologic features consisted of a diffuse interstitial fibrosis with deposits of amorphous and crystalline particles and granulomatous reaction. The identification of minerals, mainly talc, halloysite, coal and chlorite, allowed a definite diagnosis of mixed silicate pneumoconiosis to be made. This is an example of complete pathologic, mineralogic and physico-chemical analysis of a case of pneumoconiosis.

Malignant pleural mesothelioma in a female lion (Panthera leo).

An 18-year-old female lion (Panthera leo) was referred to the Department of Animal Pathology of the University of Turin (Italy). At necropsy, multiple nodular, 4-20-mm, confluent white firm nodules were scattered throughout the pleural surfaces of the thoracic wall and of the lungs. Histological lesions were represented by proliferations of papillary structures lined by cuboidal basophilic mesothelial cells with large, oval nuclei and abundant granular eosinophilic cytoplasm. Immunohistochemistry revealed immunoreactivity for pancytokeratin and vimentin. None of the cells expressed calretinin antigen. Asbestos fibers and asbestos bodies were not detected respectively by light microscopy and by Scanning Electron Microscope-Energy Dispersive Spectrometer investigations. On the contrary, chrysotile asbestos were identified in samples from shelter material. Histological and immunohistochemical findings were consistent with the diagnosis of an epithelial malignant mesothelioma. To our best knowledge, this is the first report of a pleural mesothelioma in a lion.